Is DTX2 p.Ser6Gly (c.16A>G) pathogenic?

DTX2 p.Ser6Gly (c.16A>G) is classified Uncertain significance in DTX2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-07-07). AlphaMissense: likely benign (0.0595); Very rare (popmax 0.00674%, amr).

How common is DTX2 p.Ser6Gly (c.16A>G) in the general population?

DTX2 p.Ser6Gly (c.16A>G) is very rare (popmax 0.00674%, amr) (gnomAD).

What do computational predictors say about DTX2 p.Ser6Gly (c.16A>G)?

AlphaMissense predicts likely benign (score 0.0595) — an in-silico prediction, not a clinical call.

DTX2 p.Ser6Gly

c.16A>G · VCV3505676

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0595 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00674%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0595	likely benign
REVEL	0.038	moderately benign-leaning
SaProt	LLR -6.51	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1	GERP -3.1, phastCons 0.99
Regional constraint	o/e 0.76	unconstrained · MANE · 2,592 bp · p 1.6e-06 · regional, not allelic
Overall
CADD	9.066	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00674% Admixed American · 4/59,380 alleles

Filtering AF 0.00227% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00136%

Overall 0.000551% 8/1,453,050 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00674%	14,845
African / African-American	0.00401%	24,949
European (non-Finnish)	8.5e-05%	1,175,902

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: DTX2
Protein: p.Ser6Gly
Coding: c.16A>G
MANE Select: NM_001102594
Type: single nucleotide variant
Location: chr7:76480525 (GRCh38)
Gene constraint: LOEUF 0.855 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 73.01 · 4 PDB

Full DTX2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DTX2 p.Ala422= Likely benign ★★ same type
DTX2 p.Gly515= Likely benign ★★ same type
DTX2 p.Pro484= Benign ★★ same type
DTX2 p.Ala146Asp Uncertain significance ★ ⚠ same type
DTX2 p.Ala17Thr Uncertain significance ★ ⚠ same type
DTX2 p.Ala187Ser Uncertain significance ★ ⚠ same type
DTX2 p.Ala195Ser Uncertain significance ★ ⚠ same type
DTX2 p.Ala255Gly Uncertain significance ★ ⚠ same type

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/dtx2-p-ser6gly (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown